1. Field of the Invention
The present invention relates to a pharmaceutical composition for inhibiting inflammation, especially to a pharmaceutical composition useful for arthritis.
2. Descriptions of the Related Art
Arthritis is a common chronic disease that leads to joint ache due to the degeneration of articular cartilage or the inflammation of connective tissue, and thus, affects the normal movement of the joint. According to the location and causes of the occurrence, arthritis can be classified into more than a hundred types. The most common types comprise osteoarthritis (degenerative arthritis), rheumatoid arthritis, gouty arthritis, bacterial arthritis, ankylosing spondylitis, and lupus erythmatosus.
With regards to the therapy of arthritis, the initial therapy generally adopts conservative and non-surgical methods, such as medicine treatments and injection treatments. When the initial therapy is ineffective, a surgical operation treatment will then be adopted. It has been known that medicine treatments comprise the use of steroidal anti-inflammation drugs and non-steroidal anti-inflammation drugs. Although steroidal anti-inflammatory drugs can provide a quick and effective analgesic effect, the drugs cause many side effects, such as osteoporosis, uncicatrized wounds, upper gastrointestinal bleeding, or may even aggravate the symptoms of hypertension or diabetes. Thus, these drugs are gradually excluded in the medicine treatment. As for non-steroidal anti-inflammation drugs, although they can provide a good analgesic effect, if used long term, side effects, such as peptic ulcer, lower limb dropsy, damage of kidney function, etc., may arise. Thus, non-steroidal drugs are restricted in practical application.
It has been known that hyaluronic acid (also known as hyaluronan or alduronic acid) has been widely used in injection formulations for inhibiting osteoarthritis. In this case, an injection solution containing hyaluronic acid is directly injected into a patient's joint to moderately alleviate inflammation and relive the achy feeling. The mechanism of hyaluronic acid is still unclear to date, but it has been known that hyaluronic acid also can act as a lubricant to help the movement of joints, and meanwhile, improve joint function. However, it has been discovered that although hyaluronic acid can effetely relieve ache, when entering the human body, it is possible to induce temporary inflammatory responses within several days, or even may cause chronic inflammation (see Leopold et al., Increased frequency of acute local reaction to intra-articular hylan GF-20 (Synvisc) in patients receiving more than one course of treatment. J Bone Joint Surg, 2002; 84: 1619-23; Bernardeau et al., Acute arthritis after intra-articular hyaluronate injection: onset of effusions without crystal. Ann Rheum Dis, 2001; 60:518-20; and Kroesen et al., Induction of an acute attack of calcium pyrophosphate dihydrate arthritis by intra-articular injection of hylan G-F 20 (Synvisc). Clin Rheumatol, 2000; 19:147-9, which are entirely incorporated hereinto by reference). Therefore, if a desired anti-inflammation effect can be provided by a lower dosage of hyaluronic acid, the subsequent inflammation responses induced after hyaluronic acid enters a human body can be alleviated or even can be avoided.
A method for improving a hyaluronic acid formulation has been reported. In this method, by using a chemical synthesis method, hyaluronic acid is linked to methotrexate (MTX) with anti-inflammation activity via a polypeptide to form a conjugate, and the resultant product has improved anti-inflammation effects (see Homma et al., Novel hyaluronic acid-methotrexate conjugates for osteoarthritis treatment, Bioorganic and Medicinal Chemistry, 17 (2009), 4647-4656, which is entirely incorporated hereinto by reference). However, according to the teaching of the document, a mixture obtained by simply mixing hyaluronic acid and methotrexate cannot achieve the improving effect; in other words, the synthesis of the conjugate is necessary. However, the preparation of the conjugate needs a polypeptide material and involves complicated synthesis steps, which must increase the production cost of a hyaluronic acid formulation. Thus, this method not only has difficulty in a manufacturing-scale preparation process, but also increases the economic burden of users, and accordingly, has many limitations in clinical application.
The inventors of the present invention found that a combination of vitamin and hyaluronic acid can provide an improved anti-inflammation effect, and thus, a desired anti-inflammation effect can be provided by a lower dosage of hyaluronic acid, thereby alleviating or avoiding the temporary inflammation responses induced after hyaluronic acid enters the human body.